Helicobacter cinaedi Induced Typhlocolitis in Rag‐2‐Deficient Mice

Abstract

Background Helicobacter cinaedi, an enterohepatic helicobacter species (EHS), is an important human pathogen and is associated with a wide range of diseases, especially in immunocompromised patients. It has been convincingly demonstrated that innate immune response to certain pathogenic enteric bacteria is sufficient to initiate colitis and colon carcinogenesis in recombinase-activating gene (Rag)-2-deficient mice model. To better understand the mechanisms of human IBD and its association with development of colon cancer, we investigated whether H. cinaedi could induce pathological changes noted with murine enterohepatic helicobacter infections in the Rag2−/− mouse model. Materials and Methods Sixty 129SvEv Rag2−/− mice mouse were experimentally or sham infected orally with H. cinaedi strain CCUG 18818. Gastrointestinal pathology and immune responses in infected and control mice were analyzed at 3, 6 and 9 months postinfection (MPI). H. cinaedi colonized the cecum, colon, and stomach in infected mice. Results H. cinaedi induced typhlocolitis in Rag2−/− mice by 3 MPI and intestinal lesions became more severe by 9 MPI. H. cinaedi was also associated with the elevation of proinflammatory cytokines, interferon-γ, tumor-necrosis factor-α, IL-1β, IL-10; iNOS mRNA levels were also upregulated in the cecum of infected mice. However, changes in IL-4, IL-6, Cox-2, and c-myc mRNA expressions were not detected. Conclusions Our results indicated that the Rag2−/− mouse model will be useful to continue investigating the pathogenicity of H. cinaedi, and to study the association of host immune responses in IBD caused by EHS.

NovelHelicobacterspeciesH.japonicumisolated from laboratory mice from Japan induces typhlocolitis and lower bowel carcinoma in C57BL/129 IL10−/−mice

“…and 67% of the infected mice developed GIN with dysplasia score above 3. There were no correlations with helicobacter colonization levels and the severity of pathology in H.japonicum infected IL10 −/− mice which is consistent with other EHS-induced intestinal disease in mouse models (22,25).…”

Helicobacter Species Identified in Captive Sooty Mangabeys (Cercocebus atys) with Metastatic Gastric Adenocarcinoma

“…and different than H. suis; however, our 16S rRNA sequence analysis demonstrating 95% homology to H. pullorum supports this possibility. We have recently reported that another enterohepatic helicobacter, H. cinaedi, persistently colonizes the stomach of mice [42]. This finding also emphasizes previous studies where H. cinaedi was identified in the stomachs of humans, some with gastric cancer [43,44].…”

Helicobacter saguini, a Novel Helicobacter Isolated from Cotton-Top Tamarins with Ulcerative Colitis, Has Proinflammatory Properties and Induces Typhlocolitis and Dysplasia in Gnotobiotic IL-10 −/− Mice

“…EHS infection exacerbates the onset of disease in IL-10 Ϫ/Ϫ mice and thus is a frequently used model to study pathogen-induced IBD and colon cancer. H. hepaticus and H. bilis are the most thoroughly studied EHS; however, other EHS, like H. trogontum, H. typhlonius, H. rodentium, H. mastomyrinus, and H. cinaedi, a human pathogen, can also cause IBD-like disease in immunocompromised mice (9,11,34,(38)(39)(40). Because EHS-induced colitis in IL-10 Ϫ/Ϫ mice is well characterized, we chose this mouse model to investigate the pathogenic potential of H. saguini.…”